This paper studies the nonlinear resonance of a cavity filled with a nonlinear biphasic medium made of a liquid and gas bubbles at a frequency generated by nonlinear frequency mixing. The analysis is performed through numerical simulations by mixing two source signals of frequencies well below the bubble resonance. The finite-volume and finite-difference based model developed in the time domain simulates the nonlinear interaction of ultrasound and bubble dynamics via the resolution of a differential system formed by the wave and Rayleigh–Plesset equations. Some numerical results, consistent with the literature, validate our procedure. Other results reveal the existence of a frequency shift of the cavity resonance at the difference-frequency component, which rises with pressure amplitude and evidences the global changes undergone by the bubbly medium under finite amplitudes. Finally, this work shows the enhancement of the amplitude of the difference-frequency component generated by parametric excitation using the nonlinear resonance shift, which is more pronounced when the second primary frequency is constant, the first one is varied to match the nonlinear resonance, and both have the same amplitude.