3585 Background: BRAF V600E mutation plays a negative prognostic role in metastatic colorectal cancer (mCRC) patients, leading to a median PFS of 4-6 months with first-line conventional treatments. Recently, results from a retrospective exploratory analysis suggested that an up-front intensive treatment with FOLFOXIRI plus bevacizumab could improve the outcome of BRAF mutant mCRC. Methods: Fifteen consecutive BRAF mutant mCRC patients treated with first-line FOLFOXIRI plus bevacizumab were included in a validation set. The primary endpoint was 6-months progression free rate (6m-PFR). Secondary endpoints were: overall survival, response rate and the pooled analysis of all main outcome parameters in both the exploratory and validation set. Results: In the validation set, 11 out 15 patients included were progression-free at 6 months, for a 6m-PFR of 73.3%. Primary endpoint was met. At a median follow-up of 21.6 months, median progression-free survival was 9.2 months while median OS has not yet been reached. In the pooled data analysis of the validation set and the initial retrospective cohort 24 out 25 total patients were evaluable for response: partial or complete response was obtained in 17 (68%) and in 1 (4%) patient, respectively, for an overall response rate of 72%. At a median follow-up of 34.1 months, the pooled set of patients showed a median PFS of 11.8 months and a median OS of 23.8 months. Conclusions: These data suggest that FOLFOXIRI plus bevacizumab could be a reasonable option for the first-line treatment of BRAF mutant metastatic colorectal cancer patients.