First-line FOLFOXIRI Plus Bevacizumab in BRAF Mutant Metastatic Colorectal Cancer

Inclusion Criteria: * Histologically confirmed colorectal adenocarcinoma; * Availability of formalin-fixed paraffin embedded tumor block from primary and/or metastasis; * BRAF V600E mutant status of primary colorectal cancer and/or related metastasis; * Unresectable and measurable metastatic disease according to RECIST criteria; * Male or female, aged \> 18 years and \< 75 years; * ECOG PS \< 2 if aged \< 71 years; * ECOG PS = 0 if aged 71-75 years; * Life expectancy of more than 3 months; * Adequate haematological function: ANC ≥ 1.5 x 10\^9/L; platelets ≥ 100 x 10\^9/L, Hb ≥ 9 g/dL; * Adequate liver function: serum bilirubin ≤ 1.5 x ULN; alkaline phosphatase and transaminases ≤ 2.5 x ULN (in case of liver metastases ≤ 5 x ULN); * Serum creatinine ≤ 1.5 x ULN; * Previous adjuvant chemotherapy is allowed if more than 12 months have elapsed between the end of adjuvant therapy and first relapse; * At least 6 weeks from prior extended radiotherapy and 4 weeks from surgery; * Written informed consent to experimental treatment and molecular analyses. Exclusion Criteria: * Presence or history of CNS metastasis; * Serious, non-healing wound, ulcer, or bone fracture; * Evidence of bleeding diathesis or coagulopathy; * Uncontrolled hypertension; * Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (CVA) (≤6 months before treatment start), myocardial infarction (≤ 6 months before treatment start), unstable angina, NYHA ≥ grade 2 chronic heart failure (CHF), uncontrolled arrhythmia; * Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes; * Chronic, daily treatment with high-dose aspirin (\>325 mg/day); * Symptomatic peripheral neuropathy ≥ 2 grade NCIC-CTG criteria; * Active uncontrolled infections; * Treatment with any investigational drug within 30 days prior to enrolment; * Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of curatively treated basal and squamous cell carcinoma of the skin or in situ cancer of the cervix; * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start; * Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome; * Fertile women (\< 2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception.