Background: Since FOLFIRINOX (5-fluorouracil, oxaliplatin, leucovorin and irinotecan) improved efficacy but also increased toxicity in pancreatic ductal adenocarcinoma (PDA) patients, several reports have been published about modified FOLFIRINOX as a concept of dose reduction. However, the lower limit of dose reduction is still unclear. The aim of this study is to find the minimal relative dose intensity (RDI, %) of FOLFIRINOX that can be expected to yield tumor response in advanced pancreatic ductal adenocarcinoma. Methods: A total of 95 PDA patients treated with FOLFIRINOX as a first line therapy were retrospectively reviewed. Based on Hryniuk’s arithmetic formula, we defined an extended Hryniuk’s calculation and launched a calculator site (http://www.rdicalc.com). Using receiver operator characteristic (ROC) curve, we investigated minimal RDI with a view to obtaining tumor response rate (RR) and disease control rate (DCR). The toxicity profile was also described. Results: Among the 95 patients, 85 patients completed the initial treatment until the first radiological evaluation with median 3 cycles and 56 days. Thirty one patients had locally advanced PDAC and 54 had metastatic disease. As the minimal effective thresholds, the ROC curve showed 71.5% RDI for RR (78.1% sensitivity, 83.0% specificity) and 54.5% RDI for DCR (91.3% sensitivity, 56.3% specificity). When divided by 5% units, the minimal RDI for RR and DCR was 70% and 55%, respectively. Among the 95 patients, including the dropout group, grade III/IV neutropenia, febrile neutropenia and vomiting was 45%, 13% and 31%, respectively. Early period toxicities and RDI did not show dose-response relationships. Conclusions: Although reduced dose FOLFIRINOX could be effective in advanced PDAC, our data suggest that more than 70% RDI for RR and 55% for DCR should be preserved. Toxicity rates were not influenced by RDI level in the early therapeutic period.