Background: Although FOLFIRINOX and nab-paclitaxel plus gemcitabine have improved the survival of unresectable pancreatic cancer patients, high unmet medical needs still exist for the treatment of this cancer. Nivolumab has shown efficacy for multiple cancer types in not only its monotherapy but also combinations with conventional chemotherapies. This study aimed to assess the efficacy and safety of nivolumab in combination with modified FOLFIRINOX, which is one of the first line chemotherapy for pancreatic cancer. Methods: Thirty-one treatment-naïve patients with metastatic, unresectable/recurrent pancreatic cancer patients received nivolumab (480 mg, every 4 weeks) plus modified FOLFIRINOX (oxaliplatin 85 mg/m², levofolinate 200 mg/m², irinotecan 150 mg/m² and fluorouracil 2400 mg/m², every 2 weeks). The primary endpoint was objective response rate (ORR) (central assessment). Secondary endpoints were overall survival (OS), progression-free survival (PFS) (central assessment), safety etc. Results: The median duration of follow-up was 13.40 months. ORR was 32.3% (CR: 0.0%, PR: 32.3%) and the median duration of response was 7.36 (range 3.5-20.1+) months. Median OS and PFS were 13.40 (90% CI 10.87-15.24) months and 7.39 (90% CI 3.88-7.59) months, respectively. The 1-year survival rate was 54.8 (90% CI 39.1-68.1) %. The most frequently reported grade 3-4 drug-related adverse events were neutrophil count decreased (38.7%), decreased appetite (16.1%), hypokalemia (12.9%), febrile neutropenia (9.7%), nausea (9.7%) and white blood cell count decreased (9.7%). Adrenal insufficiency (3.2%) was observed as immune mediated adverse event. Conclusions: Nivolumab in combination with modified FOLFIRINOX had a manageable safety profile in patients with metastatic pancreatic cancer. Additional work is needed to determine the population who can benefit from the combination. Clinical trial information: JapicCTI-184230.