FOLFOXIRI/BEV represents an option as 1L in mCRC patients (pts). The efficacy of immunotherapy is limited in the MSI subgroup. Combining anti-VEGF antibodies with anti-PD1/PDL1 regulators creates continuous immune stimulation. The NIVACOR was a single-arm, open-label, multicenter, phase II trial in which mCRC RAS/BRAF mut pts in 1L received NIV 240 mg, FOLFOXIRI (IRI 165 mg/m2, OXA 85 mg/m2, leucovorin 200 mg/m2, and 5-FU 3,200 mg/m2 IC for 48 h) plus BEV 5 mg/kg IV q14 days for 8 cycles and then, NIV/BEV as maintenance until PD or unacceptable toxicities. The primary endpoint was the ORR. According to Fleming’s design with alpha and beta levels of 0.05 and 0.2, in a sample size of 73 pts (comprehensive 10% drop-out rate), at least 56 responses were necessary to not reject the alternative hypothesis of an ORR=0.80. From October 2019 to March 2021, 73 pts were enrolled in 9 Italian centers. The median (m) age was 60 (51-65); 50.7% were M. The main primary tumor side was right (50.7%) and liver metastases current at 56.2%. The molecular features were: RAS mut 87.7%, BRAF mut 16.2%, both RAS/BRAF mut 4.5%; 10 (13.7%) MSI, and 63 (86.3%) MSS. On December 31, 2021, the (m) follow-up was 14.3 (IQR 11.5-16.5) months (mo) and the duration of treatment was 12 (8-17) cycles. The ORR was 76.7%: 7 (9.6%) CR and 49 (67.1%) PR; 15 (20.6%) SD with a DCR of 97.3%, and 2 (2.7%) were not evaluable. The mDoR was 8.4 mo (95%CI, 7-NE). The mPFS was 10.1 mo (95%CI, 9.4-NE) and 12-mo PFS 53.4%. At data cut-off, 65 (89.1%) pts are still alive. In MSS subgroup, the ORR was 77.8%, mDoR 7.39 mo (95% CI 6.21-9.99), DCR 96.8%, and mPFS 9.73 mo (95%CI 8.71-14.52). The surgery of the primary tumor, metastases, or both, was performed on 6 (8.2%), 9 (9.6%), and 5 (6.9%) pts. The main grade 3-4 toxicities were: neutropenia (G3 21.9%, G4 15.1%), diarrhea (G3 17.8%, G4 1.4%), hypertension and fatigue G3 in 6.8%, and febrile neutropenia G4 (4.1%). The primary endpoint was met. NIV plus FOLFOXIRI/BEV shows a good activity and safety profile. Promising activity was observed in the MSS pts. These data sustenance the conduction of a randomized-controlled phase III study.