Efficient treatment of chemical industry park tailwater remains challenging owing to the presence of refractory and toxic pollutants with low biodegradability. Although coupling advanced oxidation with biodegradation represents a promising strategy, conventional approaches often suffer from high operational costs or limited efficiency resulting from excessive or insufficient oxidation. To overcome these limitations, a pilot-scale system for the simultaneous coupling of ozonation and biodegradation (SCOB) was developed using an inner-cycle fluidized bed with a coaxial double-tube configuration, enabling near-synchronous spatial–temporal integration of the two processes. Under optimal operating conditions (ozone dosage of 15 mg/(L·h) and hydraulic retention time of 18 h), the SCOB system achieved ~70% chemical oxygen demand removal, surpassing standalone ozonation and biological processes by ~13% and ~37%, respectively. The system also achieved substantial reductions in chroma (~87%), turbidity (~94%), and ultraviolet absorbance at 254 nm (~89%) while effectively transforming refractory aromatic and sulfur-containing dissolved organic matter into more biodegradable fractions. Fourier-transform ion cyclotron resonance mass spectrometry analysis revealed significant decreases in aromaticity and unsaturation indices, confirming efficient degradation of recalcitrant organic compounds. Toxicity assays further demonstrated marked reductions in biotoxicity toward plants, luminescent bacteria, and zebrafish. Metagenomic analysis indicated enrichment of functional microbial genera (e.g., Hyphomicrobium, Aequorivita, and Roseovarius) and metabolic genes associated with aromatic and sulfur compound degradation. These findings demonstrate that the inner-cycle fluidized SCOB system effectively integrates ozone oxidation and biodegradation, offering a robust and efficient strategy for advanced treatment of chemical industry tailwater.