mFOLFOXIRI+Bev vs. mFOLFOX6+Bev for RAS Mutant Unresectable Colorectal Liver-limited Metastases

Inclusion Criteria: * Histological proof of colorectal adenocarcinoma; * Age ≥ 18 years and ≤75 years; * Simultaneous liver-limited metastases; * Initially unresectable liver metastases determined by a local MDT; * RAS mutation and BRAF V600E wild-type; * At least one measurable liver metastasis; * Initially resectable primary tumor or primary tumor already resected; * World Health Organization (WHO) performance status 0-1; * Life expectancy ≥ 3 months; * Adequate hematologic function: absolute neutrophil count (ANC)≥1.5×109/l, platelets≥100×109/l, and hemoglobin(HB) ≥ 9g/dl; * Adequate liver and renal function: total bilirubin ≤2.0 mg/dl, serum transaminases ≤ 5x upper limit of normal(ULN), and serum creatinine ≤ 1.5x ULN and creatinine clearance ≥ 30 ml/min; * Written informed consent. Exclusion Criteria: * Previous systemic treatment for metastatic disease; * Previous surgery for metastatic disease; * Extrahepatic metastases; * Unresectable primary tumor; * Major cardiovascular events (myocardial infarction, severe/unstable angina, congestive heart failure, CVA) within 12 months before randomisation; * Acute or subacute intestinal obstruction; * Second primary malignancy within the past 5 years; * Drug or alcohol abuse; * No legal capacity or limited legal capacity; * Pregnant or lactating women; * Uncontrolled hypertension, or unsatisfactory blood pressure control with ≥3 antihypertensive drugs; * Peripheral neuropathy;