Background: Induction chemotherapy (CT) is a promising option in LARC. FOLFOXIRI + BV is an effective treatment in metastatic colorectal cancer. Methods: Patients (pts) with LARC at < 12 cm from the anal verge, N+ or cT4 or high risk cT3 (MRI criteria) underwent 6 cycles of FOLFOXIRI + BV followed by CRT (50.4 Gy + 5FU 225 mg/m²/day or capecitabine 800 mg/m²/bid 5 days/week + BV 5 mg/kg on days 1, 15, 28). Surgery was planned 8 weeks after CRT. Primary endpoint is 2-year disease-free survival (DFS). Results: From April 2012 to April 2015 48 pts were enrolled. At now, 46 pts completed induction CT, 43 completed CRT and 39 underwent surgery (5 pts ongoing). Pts characteristics were: median age, 53 years (range 30-74); cT2/cT3/cT4, 4%/60%/36%; cN0/N+, 4%/96%. Main grade (G) 3/4 toxicities during induction were neutropenia (42%), febrile neutropenia (4.2%), diarrhea (12.5. Two pts did not complete induction: one died due to bowel perforation and sepsis and one discontinued CT after acute kidney injury. Response rate (RR) after induction was 77%. Forty-five pts started CRT (1 pts underwent surgery after induction because of SAE). After the first 13 patients, protocol was amended and schedule of capecitabine modified due to an excessive rate of G3 toxicities during CRT: hand-foot syndrome (23%), proctalgia (23%), proctitis (23%) and diarrhea (15%). After amendment all pts completed CRT with acceptable toxicity: G3 proctitis 6.7% and proctalgia 3.3%. One pts died due to early progressive disease (PD) after CRT. RR after CRT was 88%. Surgery was low anterior resection 87%, abdomino-perineal resection 8%, other 5%. Radical resection was achieved in 95% of pts. Early post-surgical complication rate was 31%. Pathologic complete response was reached in 33% and pathological downstaging in 44% of pts. At a median follow up of 17 months, 8 pts had PD and estimated 2y-DFS is 72%. Conclusions: Induction CT with FOLFOXIRI + BV is feasible and highly active. A protocol amendment was needed due to toxicities during CRT. The rate of early post-surgical complications is not negligible. A longer follow up is needed for DFS. Clinical trial information: 2011-003340-45.