• Be ≥18 years of age at the time of consent.

• Histologic or cytologic diagnosis of colorectal adenocarcinoma (CRC)

• Patients with advanced or metastatic CRC

• Performance status, ECOG: 0, 1

• For dose escalation phase: patients with CRC where FOLFIRI+ bevacizumab is considered appropriate standard therapy (previously treated with FOLFOX based regimen in advanced/metastatic CRC is allowed). For dose expansion phase: patients must not have received 5FU-based therapy previously for metastatic disease. Patients who received FOLFOX/CAPOX regimens in the neoadjuvant/adjuvant setting are allowed if recurrence free survival is at least 1 year or longer since completion of adjuvant therapy.

• Presence of a metastatic lesion that can be safely biopsied for correlative assays (Only for FOUR patients enrolling on the dose expansion phase).

• Patient must meet the following laboratory values at the screening visit:

‣ Absolute Neutrophil Count ≥1.5 x 109/L

⁃ Platelets ≥100 x 109/L

⁃ Hemoglobin (Hgb) ≥9 g/dL

⁃ Creatinine Clearance ≥60 mL/min using Cockcroft-Gault formula

⁃ Total bilirubin ≤1.5 x ULN

⁃ Aspartate transaminase (AST) ≤2.5 x ULN, except for subjects with liver metastasis, who may only be included if AST ≤5.0 x ULN

⁃ Alanine transaminase (ALT) ≤2.5 x ULN, except for subjects with liver metastasis, who may only be included if ALT ≤5.0 x ULN

⁃ Urine dipstick reading for proteinuria \< 2+. Participants having ≥ 2+ proteinuria on urine dipstick testing at baseline will undergo a 24-hour urine collection for quantitative assessment of proteinuria and must demonstrate \< 1 g of protein in 24 hours. Participants with urine protein ≥ 1 g per 24 hours will be ineligible

• Blood pressure \<=160/100 mm Hg

• Presence of measurable disease by RECIST 1.1 criteria within 28 days prior to the first dose of study treatment.

⁃ Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0- 1 (Appendix A-Performance Status Criteria).

⁃ Normal ECG defined as the following: QTcF at screening \<450 ms (male subjects), \<460 ms (female subjects)

⁃ Before enrollment, a woman must be either:

• Not of childbearing potential: postmenopausal (\>45 years of age with amenorrhea for at least 12 months or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone (FSH) level \>40 IU/mL); permanently sterilized (eg, tubal occlusion, hysterectomy, bilateral salpingectomy); or otherwise be incapable of pregnancy.

∙ Of childbearing potential and practicing (during the study and for 6 months after receiving the last dose of study agent for women and 3 months after receiving the last dose of study agent for men)) a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies: e.g., established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS); barrier methods; true abstinence (when this is in line with the preferred and usual lifestyle of the subject).

∙ Note: If the childbearing potential changes after start of the study (eg, woman who is not heterosexually active becomes active) a woman must begin a highly effective method of birth control, as described above.

⁃ A woman of childbearing potential must have a negative serum (β-human chorionic gonadotropin \[β-hCG\]) or urine pregnancy test at screening.

⁃ During the study and for 6 months after receiving the last dose of study agent, a woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction.

⁃ A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control e.g., either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 3 months after receiving the last dose of study drug.

⁃ Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent and privacy language as per HIPAA must be obtained from the subject or legally authorized representative (if applicable) prior to any study- related procedures

⁃ Sign an informed consent document indicating that they understand the purpose of and procedures required for the study, are willing to participate in the study, and are willing and able to adhere to the prohibitions and restrictions specified in this protocol. Informed consent must be obtained before performing any study specific procedures.

⁃ As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study

⁃ Subject agrees not to participate in another interventional study while receiving study drug in present study