• All subjects are required to sign an informed consent form before starting the study-related procedure

• Age 18-75 years old, male or female.

• have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1, life expectancy \>3 months.

• Histologically or cytological proven metastatic or recurrent adenocarcinoma of the colon or rectum.

• Prior treatment with a fluoropyrimidine (5-fluorouracil \[5-FU\] or capecitabine) and oxaliplatin with bevacizumab or cetuximab targeted therapy as the first-line regimen.

• Recurrence or metastasis within 12 months after completion of adjuvant/neoadjuvant therapy with oxaliplatin and fluoropyrimidine-based drugs is also considered as the failure of first-line chemotherapy.

• At least one measurable metastatic lesion, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

• Adequate organ function: bone marrow, kidney, liver function (within 7 days before treatment start) Absolute neutrophil count ≥ 1.5×109/L Platelet count ≥ 100×109/L Hemoglobin≥ 90g/L (no history of blood transfusion within 7 days); Creatinine clearance≥ 60 ml/min (Cockcroft-Gault formula) Bilirubin ≤ 1.5 x the upper limit of normal (ULN) Glutamate aminotransferase (AST)/ alanine aminotransferase (ALT) levels ≤2.5 x ULN or =\< 5 x ULN if with hepatic metastases; Alkaline phosphatase (AKP) ≤ 2.5 x ULN or =\< 5 x ULN if with hepatic metastases;

• Urine protein \<1+ or 24-hour urine protein \<1 gram;

⁃ International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN or within the range if receiving anticoagulant therapy;

⁃ Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence; IUDs, etc) during the study period and within 90 days of the last study medication. All female patients will be considered fertile unless they have spontaneous menopause, artificial menopause, or sterilization (e.g., hysterectomy, bilateral adnexectomy, or radiation ovarian irradiation).