A general nonlinear response theory is derived for an arbitrary time-dependent Hamiltonian, not necessarily obeying time-reversal symmetry. We consider the application of this theory to a multiterminal mesoscopic system with arbitrary interactions and time-dependent voltages. This allows us to obtain a generalized Kubo-type formula. We derive a microscopic expression for the finite frequency differential conductance matrix, which preserves current conservation and gauge invariance. We exploit this result to show that the asymmetric part of the current fluctuation matrix at finite frequency obeys a generalized time-dependent fluctuation-dissipation theorem. In the stationary regime, this theorem provides a common explanation for the asymmetry of the excess noise with respect to positive and negative frequencies that has been obtained in several systems as a consequence of nonlinearity. It also explains the origin of the unexpected negative sign of the excess noise. Finally, we apply these general results to the case of a tunnel junction and obtain a nonperturbative out-of-equilibrium link between conductance and current fluctuations. We also derive a universal property of the finite frequency noise in the perturbative regime.