Futibatinib is a novel FGFR inhibitor currently under investigation as a second-line treatment for locally advanced or metastatic cholangiocarcinoma harboring FGFR2 gene fusions and rearrangements. As FGFR-targeted therapies move into the frontline setting, sequencing of these drugs remains undetermined. To date, no study has investigated the use of futibatinib in the context of pemigatinib resistance. We describe a 50-year-old woman with metastatic FGFR-aberrant intrahepatic cholangiocarcinoma who showed a robust response to futibatinib for 23.6 months, having previously benefited from pemigatinib. Futibatinib was safely used despite her history of decompensated cirrhosis and significant cytopenias. We observed a reduction in CA 19-9 level and a partial radiographic response on futibatinib. Serial next-generation sequencing and cell-free DNA testing proved crucial to making appropriate treatment decisions.