Chemodynamic therapy (CDT) has shown potential for important applications in tumor precision therapy, but insufficient endogenous hydrogen peroxide (H2O2), overexpressed glutathione (GSH) and a weak Fenton-reaction rate greatly reduced the efficacy of CDT. Herein, a metal-organic framework (MOF) based bimetallic nanoprobe with self-supplying H2O2 was developed for enhancing CDT with triple amplification, in which ultrasmall gold nanoparticles (AuNPs) were deposited on Co-based MOFs (ZIF-67), and manganese dioxide (MnO2) nanoshells were coated to form a ZIF-67@AuNPs@MnO2 nanoprobe. In the tumor microenvironment, MnO2 depleted overexpressed GSH to produce Mn2+, and the bimetallic Co2+/Mn2+ nanoprobe accelerated the Fenton-like reaction rate. Moreover, by catalyzing glucose via ultrasmall AuNPs, the self-supplying H2O2 further promoted hydroxyl radical (˙OH) generation. Compared with those of ZIF-67 and ZIF-67@AuNPs, the ˙OH yield of ZIF-67@AuNPs@MnO2 obviously increased, due to which the cell viability decreased to 9.3%, and the tumor completely disappeared, indicating the enhanced CDT performance of the ZIF-67@AuNPs@MnO2 nanoprobe.