This is a single arm, open label trial to assess the safety and efficacy of NALIRIFOX in Japanese participants who have not previously received therapy for metastatic adenocarcinoma of the pancreas. Forty-one participants will receive the treatment NALIRIFOX (liposomal irinotecan, 5-fluorouracil, levoleucovorin and oxaliplatin) until progression or unacceptable toxicity. Anti-tumor activity will be evaluated in terms of objective response rate according to RECIST v1.1 by independent central review. Safety will be carefully monitored, with a dedicated Safety Monitoring Committee reviewing the data from the initial six participants to safeguard the well-being of all individuals involved in the study. Other evaluations will include pharmacokinetics and the relationship between mutations in the UGT1A1 genes and safety. This study aims to show that the results of the NAPOLI 3 study in the global population can be reproduced in the Japanese population.