Background: KRAS/NRAS/BRAF genotypes guide tailoring of first and subsequent lines of MCRC treatment strategy. First line triplet chemotherapy/BEV associations significantly improved progression-free survival (PFS) and overall survival (OS) in overall MCRC patients. OS may be significantly worse in the prevalent KRAS c.35 G > A and BRAFmutant (mt). Evaluation of differential clinical outcome in overall MCRC patients will help identify clinically relevant biomarkers to personalize treatment strategy. Methods: Tumoral samples of 67 MCRC pts treated with FIr-B/FOx (77% overall) were analyzed through a 50 genes panel (PGM/Colon Lung Cancer) by ION Torrent: 58 (86.5%) primary, 9 (13.4%) metastatic samples; 60 (89.5%) pre-, 7 (10.4%) post-treatment. KRAS, NRAS and BRAFcoding frames were analysed. Molecular diagnostic criteria for mutation detection: > 50% coverage; > 1% mutant allelic fraction. Clinical outcomes (PFS and OS) were evaluated and compared by log-rank. Results: Mutant KRAS_2-4/NRAS_2-4/BRAF MCRC patients were 49 (73.1%): KRAS 42 (62.6%), NRAS 15 (22.3%), BRAF 5 (7.4%). BRAF mutations were all atypical and concomitant with KRAS and/or NRAS mutations. At median follow-up 21 months (m), overall PFS and OS were 13 and 27m, and KRAS exon 2 wild-type (wt)/mt PFS 14/12m, and OS 28/21m, respectively, consistent with previously reported, and not significantly different. KRAS_2-4/NRAS_2-4/BRAF wt/mt, PFS 18/12m, OS 28/22m, not significantly different: KRAS_2-4 wt/mt, PFS 13/12m, OS 27/27m, not significantly different; NRAS_2-4 wt/mt, PFS 16/12m, OS 28/22m, not significantly different; c.35 G > A KRAS mt showed trendy worse PFS/OS 8/14m, respectively; BRAFmt/wt trendy worse PFS 8 vs 14m and OS 11 vs 28m. Conclusions: Retrospective analysis of clinical outcome of MCRC patients treated with intensive first line BEV added to triplet chemotherapy FIr-B/FOx seems to be not significantly affected by KRAS/NRAS/BRAF genotype.