Background: The outcome for mCRC has changed since the introduction of new chemotherapy schedules and targeted therapies, however new predictive biomarkers are needed. bCTCs and BRAF / PIK3CA mutations have been studied as a potential predictive biomarkers. The primary endpoint was progression-free survival (PFS) in pts WT KRAS and <3 bCTCs, according to BRAF/PIK3CA status. Methods: This is an open, multicentric, randomized phase II trial and included wildtype KRAS mCRC pts (RAS after approval of protocol amendment), younger than ≤70 with <3 bCTCs, ECOG 0-1 and available tissue for molecular analyses. Pts were stratified per number of metastatic organs involved (1 vs>1) and mutation status of BRAF and/or PIK3CA (WT vs MUT) and randomized to group A (FOLFIRI+Bev) or group B (FOLFIRI+Cet). Results: 240 pts (196 WT and 44 MUT: 6 BRAF, 12 PIK3CA and 6 BRAF + PIK3CA) were included. General characteristics per mutation status (WT vs MUT): Mean age (59 vs 61 years), gender (Male/Female 68/32 vs 70/30%), ECOG 0/1 (57/43 vs 66/34%), primary tumor unresected (48 vs 64%), RAS MUT in 12 pts (11 and 1 pts, respectively), previous chemotherapy (12 vs 9%). Overall response rate (ORR) was 52 and 41% in the WT and MUT groups, respectively. PFS and overall survival (OS) are presented in the table. Conclusions: In the low risk mCRC pts according to bCTCs, BRAF and/or PIK3CA MUT have a negative impact in OS and a trend to worse PFS in the ITT population. The impact of treatment is under evaluation and will be provided during the meeting. Clinical trial information: 2012-000840-90.