FOLFOXIRI Compared to FOLFOX in First Line Treatment of Metastatic Colorectal Cancer

Inclusion Criteria: * Signed informed consent obtained before any study specific procedures. -Subjects must be able to understand and willing to sign a written informed consent. * Male or female subjects ≥ 18 years ≤ 75 years of age * Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 2.(ECOG PS 0-2 for≥18 years ≤ 65 years of age ，ECOG PS 0-1 for \>65 years of age) * Histological or cytological documentation of adenocarcinoma of the colon or rectum. All other histological types are excluded. * There must be documentation by PET/CT scan, CT scan, MRI, or intraoperative palpation (at the time of resection of the primary colorectal tumor, if applicable) that the patient has evidence of metastases (Histologic confirmation of metastasis is not required.). * At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria measured within 4 weeks prior to registration. * No previous chemotherapy or target therapy for metastatic disease (adjuvant chemotherapy for non-metastatic disease is allowed if terminated more than 6 months ago). * In case of previous radiotherapy, at least one measurable lesion should be located outside the irradiated field. * Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment: * 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. * Alkaline phosphatase limit ≤ 5x 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: * Previous palliative chemotherapy for metastatic disease，previous adjuvant chemotherapy including irinotecan or oxaliplatin within 6 months before random assignment. * Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization. * Life expectancy \> 12 weeks; * Extended field radiotherapy within 4 weeks or limited field radiotherapy within 2 weeks prior to randomization. Subjects must have recovered from all therapy-related toxicities. * Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks before start of study medication. * Congestive heart failure ≤ New York Heart Association (NYHA) class 2. * 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. * History of interstitial pneumonitis or pulmonary fibrosis * Pregnancy or lactation at the time of study entry. * 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. * Active inflammatory bowel disease or other bowel disease causing chronic diarrhoea * 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. * Continuous use of immunosuppressive agents (except the use of corticosteroids as anti-emetic prophylaxis/treatment).