• The patient must have histologic or cytologic evidence of a RAS colorectal cancer of adenocarcinoma or poorly differentiated histology and must have disease that is resistant to or relapsed following available standard systemic therapy or for which there is no standard systemic therapy or reasonable therapy likely to result in clinical benefit or if such therapy has been refused by the patient.

• The patient must have advanced disease, defined as cancer that is either metastatic or locally advanced and unresectable (and for which additional radiation therapy or other locoregional therapies are not considered feasible).

• Pathologically documented adenocarcinoma or poorly differentiated locally advanced/metastatic colorectal cancer

• Have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by the Investigator

• Adults ≥18 years

• Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 1

• Adequate cardiac function, as defined by left ventricular ejection fraction (LVEF) ≥45%

• Adequate organ function

• Prothrombin time ≤1.5 x ULN or international normalized ratio within ≤1.5; and either partial thromboplastin time or activated partial thromboplastin time ≤1.5 x ULN. Patients on warfarin may be included if on a stable dose with a therapeutic INR \<3.5

⁃ For the expansion stage only, patients must have a tumor that is laboratory-confirmed to be RAS mutant.

• Must have received only one prior standard of care oxaliplatin-containing regimen for locally advanced/metastatic colorectal cancer (CRC)

• Must have received prior treatment with pembrolizumab or an FDA approved PD-1/L1 inhibitor as well, if the patient has dMMR/MSI-H colorectal cancer

• May have received prior treatment with bevacizumab, cetuximab, or panitumumab, or an FDA approved biosimilar.

⁃ To be enrolled in this substudy, patients must meet all of the following criteria during the screening period:

⁃ The patient has signed informed consent prior to initiation of any study-specific procedures or treatment.

⁃ The patient must have previously untreated metastatic colorectal adenocarcinoma, defined as cancer that is metastatic and for which additional radiation therapy or other locoregional therapies in curative intent are not considered feasible or beneficial. Note that patients who have had previous systemic anticancer therapy as neoadjuvant or adjuvant therapy and had a metastatic recurrence at least 12 months after the last dose of adjuvant oxaliplatin will also be eligible.

⁃ The patient must have a tumor that is laboratory-confirmed to be RAS-mutant based on the tumor tissue analysis. RAS-mutant status confirmation by liquid biopsy is acceptable only if the tumor sample is not available. For patients with newly diagnosed disease, RAS-mutant status must be obtained before initiation of therapy.

⁃ The patient must have disease that is measurable by standard imaging techniques by RECIST version 1.1 or by physical examination methods (ruler or calipers). For patients with prior radiation therapy, measurable lesions must be outside of any prior radiation field(s), unless disease progression has been documented at that disease site subsequent to radiation.

⁃ The patient is ≥ 18 years old.

⁃ The patient has an ECOG Performance Score of ≤ 1.

⁃ The patient has adequate baseline organ function, as demonstrated by the following:

• Serum creatinine ≤ 1.5 x institutional ULN and calculated creatinine clearance \> 50 mL/minute;

∙ Serum albumin ≥ 2.5 g/dl;

∙ Bilirubin ≤ 1.5 x institutional ULN or ≤ 2.5 x institutional ULN for patients with known Gilbert's disease;

∙ AST and ALT ≤ 2.5 x institutional ULN; patients with hepatic metastases may have AST and ALT ≤ 5 x institutional ULN;

∙ ANC ≥ 2.0 x 109/L;

∙ Hemoglobin ≥ 8 g/dL and no RBC transfusions during 14 days before the start of study treatments;

∙ Platelet count ≥ 100 x 109/L and no platelet transfusions during 14 days before the start of study treatments.

⁃ For patients not taking anticoagulation therapy: INR ≤ 1.5 or PT ≤ 1.5 x ULN; and either PTT or aPTT ≤ 1.5 x ULN. Patients on warfarin/anticoagulation therapy may be included if on a stable dose with a therapeutic anticoagulation range.

⁃ The patient has a LVEF ≥ 45% as determined by either ECHO or MUGA scanning.

‣ If the patient is a WOCBP, she has had a negative serum or urine pregnancy test within 2 weeks prior to treatment.

‣ Men and WOCBP agree to use acceptable contraceptive methods for the duration of time on the study and continue to use acceptable contraceptive methods for at least 6 months after the last dose of bevacizumab or 2 months after the last dose of ompenaclid, whichever is later.

‣ The patient is able to adhere to the study visit schedule and other protocol requirements.