Phototherapy has garnered worldwide attention for its minimal invasiveness, controllability, and spatial selectivity in treating cancer. One promising approach involves the use of near-infrared dye IR780, which demonstrates both photodynamic therapy (PDT) and photothermal therapy (PTT) effects under 808 nm laser irradiation. However, this hydrophobic dye's toxicity and limited tumor targeting ability severely hamper its suitability for cancer applications. Herein, a biocompatible nanoplatform CoOOH-IR780@BSA (CoIRB) is developed to efficiently deliver IR780 and provide multi-mode treatments for colon tumors. Due to the nanocarrier coating, CoIRB nanoparticles demonstrated reliable dispersion and stability, and their biotoxicity was substantially reduced for safer blood circulation, which overcame the biological barrier of IR780. The nanoplatform has also shown considerable results in phototherapy in vivo and in vitro experiments, with successful inhibition of MC38 tumor growth through intravenous administration. Additionally, the introduction of cobalt ions could induce Fenton-like reactions to activate the production of toxic hydroxyl radicals (˙OH), exerting an assisted chemodynamic therapy (CDT) effect. Notably, these nanodrugs also exhibited potential as scavengers of reductive glutathione (GSH) and hydrogen sulfide (H2S), leading to amplifying oxidative damage of reactive oxygen species (ROS). Overall, the versatile therapeutic platform, CoIRB, has opened up considerable prospects as a biotherapeutic option for combining PDT/PTT/CDT against colon cancer.