Pancreatic cancer exhibits profound chemoresistance resulting either from pre-existing (intrinsic) mechanisms, or from anticancer drug treatment itself (acquired chemoresistance). We present the case of a patient with pancreatic adenocarcinoma metastatic to the liver who experienced clinical, radiographic and tumor marker response to three lines of gemcitabine-based chemotherapy. The regimens included: 8 cycles of gemcitabine and oxaliplatin (GEMOX), 8 cycles of gemcitabine, docetaxel and capecitabine (GTX) and more than 3 cycles of gemcitabine and nab-paclitaxel, with an exceptional response 2 years from the initiation of chemotherapy for metastatic pancreatic cancer.