Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), combined with fluoropyrimidine-based chemotherapy is now the standard first and second-line treatment for metastatic colorectal cancer. The efficacy of bevacizumab with cytotoxic agents in the third-line treatment of patients with mCRC is still unknown.

This is a single arm, phase II, open-labelled clinical trial to evaluate the safety and efficacy of bevacizumab combined with cytotoxic agents in the treatment of patients with mCRC progressing under all available cytotoxic chemotherapy

Inclusion Criteria:

• Signed informed consent obtained.
• Subjects must be able to understand and willing to sign a written informed consent.
• Subjects > 18 years of age
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 2.
• Histological or cytological diagnosis of adenocarcinoma of the colon or rectum.
• Subjects have unresectable metastatic lesions.
• Subjects failed to respond to oxaliplatin, irinotecan and fluorouracil.
• Subjects have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria measured within 4 weeks prior to registration.
• Leukocytes ≥ 3.0 x109/ L, absolute neutrophil count (ANC) ≥ 1.5 x109/ L, platelet count ≥ 100 x109/ L, hemoglobin (Hb) ≥ 9g/ dL.
• Total bilirubin ≤1.5 x the upper limit of normal (ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN.
• Amylase and lipase ≤ 1.5 x the ULN.
• Serum creatinine ≤ 1.5 x the ULN.
• Calculated creatinine clearance or 24 hour creatinine clearance ≥ 50 mL/ min.

Exclusion Criteria:

• Any previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to this study.
• Extended field radiotherapy within 4 weeks or limited field radiotherapy within 2 weeks prior to randomization.
• Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks before start of study medication.
• Uncontrolled hypertension. (systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management).
• Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment or a history of ventricular arrhythmia
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months before start of study medication.
• Any evidence of active infection.
• Known history of human immunodeficiency virus (HIV) infection.
• History of bleeding diathesis or coagulopathy.
• History of interstitial pneumonitis or pulmonary fibrosis
• Pregnancy or lactation at the time of study entry.
• Any history of or currently known brain metastases.
• Known dihydropyrimidine dehydrogenase (DPD) deficiency
• Any illness or medical conditions that are unstable or could jeopardize the safety of the subjects and his/her compliance in the study.
• Subjects with known allergy to the study drugs or to any of its excipients.
• Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.