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.