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Background: Doublets plus bev are a standard option for the first-line treatment of mCRC.First-line FOLFOXIRI demonstrated superior RR,PFS and OS compared to FOLFIRI.A phase Ⅱ study of FOLFOXIRI/bev showed promising activity and manageable toxicities.The objective of the TRIBE trial was to confirm the superiority of FOLFOXIRI vs FOLFIRI when bev is added to chemotherapy(CT).Methods: Eligibility criteria included: measurable and unresectable mCRC,age 18-75 years,no prior CT for advanced disease.Pts were randomized to either FOLFIRI/bev(arm A)or FOLFOXIRI/bev(arm B).Both treatments were administered for a maximum of 12 cycles followed by 5FU/bev until progression.Primary endpoint was PFS.Results: Between July 2008 and May 2011 508 pts were randomized.Pts characteristics were(arm A/arm B): median age 60/61,ECOG PS 1-2 11%/10%,synchronous metastases 81%/79%,multiple sites of disease 74%/70%,liver-only disease 18%/23%,prior adjuvant(adj)12%/12%.At a median follow-up of 26.6 mos 424 pts progressed and 244 died.Median PFS and OS in the intention to treat(ITT)population were 10.9 and 30.9 mos.FOLFOXIRI/bev significantly increased PFS(median 9.7 vs 12.2 mos,HR 0.73 [0.60-0.88] p50.0012).Subgroup analyses based on stratification factors(PS,prior adj)and baseline characteristics(site of primary,liver only disease,resection of primary,Kohne score)did not evidence significant interactions between treatment and analyzed factors.A trend toward a more consistent effect of FOLFOXIRI/bev was reported in no prior adj(HR 0.68 [0.55-0.83])compared to prior adj group(HR 1.18 [0.67-2.08],p for interaction50.071).Response rate(RECIST)was also significantly improved(53%vs 65%p50.006).FOLFOXIRI/bev did not increase the R0 secondary resection rate in the ITT population(12%vs 15%,p50.327),or in the liver-only subgroup(28%vs 32%,p50.823).Conclusions: FOLFOXIRI/bev compared to FOLFIRI/bev,significantly increases PFS and response rate.Subgroup analysis suggests a possible interaction between prior adj CT and PFS benefit.Secondary resection rate does not differ between treatment arms.