Background: Pancreatic cancer has one of the poorest prognoses of all solid tumours with median overall survival rate between 9 and 12 months worldwide. (1, 2) Treatment guidelines beyond first line chemotherapy are subsequently limited by a paucity of data. Modified oxaliplatin, irinotecan, 5-fluorouracil and leucovorin (mFOLFIRINOX) has been used historically as second line chemotherapy but is not yet standard of care. (3) Patients are often excluded from use of second line FOLFRINOX due to age or performance status. Previous studies have recognized safe use of mFOLFIRINOX in patients with ECOG 0-1 and age below 75 years but there is limited evidence for other patient populations. (4) We first reported successful use of mFOLFIRINOX for pancreatic cancer in 2014 and reviewed the outcomes from this centre in 2019. (4,5) A promising response was seen for second line mFOLFIRINOX in patients with an ECOG of 2 or less. (5) We aim to provide further evidence of the efficacy of mFOLFIRINOX in second line treatment of pancreatic cancer using a larger dataset. Methods: A retrospective review was completed of all patient records for those treated for pancreatic cancer in a single centre in Western Australia between 2008 and 2022. We identified 258 patients treated for pancreatic cancer, 110 of whom received mFOLFIRINOX as second line treatment. Kaplan Meier method was used for calculation of overall survival with 32 patients included as censored data. Results: We identified 110 patients with either locally advanced or metastatic pancreatic cancer aged between 34 and 82 years. A large number (n = 32) of patients were over the age of 70. The majority of patients had metastatic disease at presentation (56%). Almost all patients (n = 109) had gemcitabine with nab-paclitaxel as first line chemotherapy, nineteen of whom received it as part of a clinical trial combination. Median overall survival was 28 and 18 months for locally advanced and metastatic pancreatic cancer respectively. The overall survival for both groups was 20 months with a range of 4-81 months. One year survival was 82%, 3 year survival was 23% and 5 year survival was 5% for this group. Median time maintained on second line mFOLFIRINOX was 5 months with a range of 1 to 36 months. Almost half (n = 50) of the patients went on to have third line chemotherapy, nineteen of whom had third line gemcitabine/abraxane. The dose intensity of m-FOLFIRINOX was 65% for oxaliplatin, 68% for irinotecan, 18% for bolus 5-fluorouracil (5-FU) and 68% for infusional 5-FU. Conclusions: This study is the largest retrospective review of second line mFOLFIRINOX chemotherapy for pancreatic cancer reported. It provides further evidence of the efficacy of second line mFOLFIRINOX for suitable patients with advanced pancreatic cancer and suggests ECOG 2 should not be a barrier to effective treatment in this group.