Background: Several randomized trials demonstrated that intensifying the upfront chemotherapy in combination with bev is beneficial for mCRC patients with an increased incidence of some adverse events. All trials had primary endpoints other than OS, and a proper estimation of the magnitude of the OS benefit from FOLFOXIRI/bev versus doublets (FOLFIRI or FOLFOX)/bev is currently lacking. Within each trial, subgroup analyses failed to identify predictors of benefit from the intensified therapy. To test OS with higher power compared to single trials, and to explore interaction of treatment effect with main patients’ and disease characteristics, we performed an IPD meta-analysis. Methods: IPD were collected from 5 randomized trials: CHARTA (NCT01321957), OLIVIA (NCT00778102), STEAM (NCT01765582, only combined FOLFOXIRI/bev and FOLFOX/bev arms), TRIBE (NCT00719797) and TRIBE2 (NCT02339116). Primary endpoint was OS. Secondary endpoints included PFS, objective response rate (ORR), R0 resection rate, G3/4 adverse events, and subgroup analyses. All statistical analyses were by intention-to-treat, stratified by trial. Results: 1697 pts randomized to FOLFOXIRI/bev (N=846) or doublets/bev (N=851) were included. Among pts in the doublets/bev group, 595 (70%) received FOLFOX/bev and 256 (30%) FOLFIRI/bev. At a median follow up of 39.9 mos, pts assigned to FOLFOXIRI/bev reported significantly longer OS than those assigned to doublets/bev (median OS 28.9 vs 24.5 months; HR 0.81 [95%CI 0.72-0.91], p<0.001), with no significant heterogeneity among trials (p=0.39; I²=2%). The estimated 5-yr OS was 22.3% vs 10.7% (p<0.001). No significant interaction effect between treatment arm and OS was demonstrated in terms of metastatic spread (liver-limited vs. not liver-limited p=0.665), primary side (p=0.656), and RAS/BRAF status (p=0.337). Pts assigned to FOLFOXIRI/bev achieved longer PFS (median PFS 12.2 vs 9.9 months; HR 0.74 [95%CI 0.67-0.82], p<0.001), higher ORR (64.5% vs 53.6%, p<0.001), higher R0 resection rate (16.4% vs 11.8%, p=0.007), and experienced higher rates of G3/4 neutropenia (p<0.001), febrile neutropenia (p=0.019), mucositis (p=0.024), nausea (p=0.016), and diarrhea (p<0.001). Conclusions: FOLFOXIRI/bev determines a clinically and statistically significant improvement of mCRC patients’ OS vs doublets/bev with a meaningful effect also on 5-yr OS, PFS, ORR and R0 resection rate. No significant heterogeneity among explored subgroups was found.