The moment Lou asked whether or not she wanted to know why he acted out of his character, Iris knew, there was something serious behind the reason of this nagging feeling.
Iris was reassured when Cane finally opened up to her and did not reject her advance, he became affectionate with her again, but once Cane went away and the butterfly in her stomach stopped fluttering its wings, that weird feeling came again.
Especially after she saw Lou.
In the past, no matter how she tried to push him away, he would stick to her and never miss the opportunity to one up Cane.
Therefore, when she saw Lou was acting weird toward her, she knew Cane was hiding something and for odd reason, Lou agreed with him, therefore he avoided her, since he couldn't resist not to tell her.